10,000 patients and six years in the making, Novartis’s Cantos study of canakinumab has come to naught. Even focusing on a subgroup of high responders could not get the drug past the US FDA in cardiovascular disease.
Still, Novartis, which slipped news of a US complete response letter for canakinumab into its third-quarter earnings report today, already has another avenue on which to focus its R&D efforts: cancer. A surprise finding at last year’s European Society of Cardiology meeting spurred the company to start several clinical trials in oncology, with a focus on lung tumours.
At the moment, Novartis is not saying much about the CRL – which is perhaps understandable as, according to executives on its third-quarter call, it only received the letter yesterday.
But canakinumab's future in cardiovascular disease does not look promising. Novartis’s chief executive, Vas Narasimhan, admitted that the FDA had asked for additional data, but would not be drawn on whether this might mean another trial.
His mind might already be on the probably more lucrative cancer indications; studies here are on track, according to the chief exec. Unfortunately the most relevant trials in this setting are not due to yield results until 2021 and the drug, which is already approved for several rare diseases, is due to come off patent in 2024.
|Ongoing canakinumab cancer trials|
|NCT03447769||Adjuvant monotherapy; resected NSCLC||1,500||Recruiting||Aug 2021|
|Canopy 1, NCT03631199||Plus Keytruda/chemo; untreated metastatic NSCLC||627||Not yet recruiting||May 2021|
|Canopy 2, NCT03626545||Plus docetaxel; 2/3L NSCLC||240||Not yet recruiting||Mar 2021|
|NCT02900664||Spartalizumab + various therapies inc. canakinumab; NSCLC, CRC, TNBC||432||Recruiting||Jan 2020|
Canakinumab, which first got the go-ahead in 2009, is marketed as Ilaris for conditions including juvenile idiopathic arthritis.
Novartis had hoped for bigger things and a surprise win in the Cantos trial suggested that the drug could be used to reduce the risk of cardiovascular events in patients who had recently suffered a myocardial infarction, with the company homing in on a subset of high responders: patients with high-sensitivity C-reactive protein (hsCRP) levels of below 2mg/l after three months of canakinumab therapy (Novartis homes in on heart biomarker for canakinumab, 14 November 2017).
Cantos also found a decrease in cancer deaths, with the reduction looking strongest in lung cancer, so at least if canakinumab has no future in cardiovascular disease the company has that intriguing finding to pursue.
A nod in cancer might help Novartis maintain the high price for canakinumab, which costs around $200,000 per year in its currently approved indications, Bernstein analysts have estimated. There were questions about how the company would be able to justify this price tag in cardiovascular disease.
Of course, Cantos was not a cancer trial, so its findings will need to be replicated if canakinumab is to have any future outside rare diseases. And the new programme, enrolling close to 3,000 patients, will not come cheap. It will be a while before it becomes evident whether Novartis is throwing good money after bad.